α2‐Adrenoceptors Mediate Inhibition of Cyclic AMP Production in the Spinal Cord After Stimulation of Cyclic AMP with Forskolin but Not After Stimulation with Capsaicin or Vasoactive Intestinal Peptide

Abstract

In slices obtained from the ventral and the dorsal guinea pig spinal cord both forskolin and vasoactive intestinal peptide (VIP) caused a dose-dependent stimulation of the production of cyclic AMP. By contrast capsaicin stimulated cyclic AMP formation only in the dorsal cord; no effect was observed in the ventral cord. The alpha 2-adrenergic agonist UK-14,304 dose-dependently inhibited the production of cyclic AMP in both the dorsal and ventral aspects of the cord when the formation of cyclic AMP had been stimulated with 3 microM forskolin, the maximal inhibition amounting to 25-32%. Also the basal (i.e., unstimulated) production of cyclic AMP was inhibited, the inhibition amounting to about 16-18%. However, after stimulation of cyclic AMP formation in the dorsal cord with capsaicin, UK-14,304 was virtually ineffective in inhibiting the accumulation of cyclic AMP. Also, when the formation of cyclic AMP was stimulated with VIP, UK-14,304 was virtually ineffective in inhibiting the formation of cyclic AMP both in the ventral and the dorsal parts of the cord. When cyclic AMP production had been stimulated with forskolin the ability of UK-14,304 to inhibit the formation of cyclic AMP was not attenuated by capsaicin, either in the ventral or in the dorsal cord. The results are discussed with the notion that cyclic AMP inhibitory spinal cord alpha 2-adrenoceptors are located on cells accessible to stimulation of cyclic AMP with forskolin but not with capsaicin or VIP.